Advances in Radio-Frequency Transdermal Drug Delivery

A microelectronic system based on radio-frequency (RF) cell ablation addresses limitations of other transdermal drug-delivery methods. This system expands the transdermal spectrum to include the delivery of water-soluble molecules, peptides, proteins, and other macromolecules.

Passive transdermal drug delivery has been used for more than 20 years, but faces certain limitations with the type of active molecules that may delivered through this route. Very few drugs can passively diffuse across the skin barrier at therapeutically useful rates. Cell ablation using a radio-frequency (RF) alternating electrical current is a well known, proven medical technology that can be applied to drug delivery to overcome this obstacle. RF ablation is a safe, low-cost technique and a familiar concept in medical practice. When properly modified, RF cell-ablation technology may also create microchannels in the skin's surface to enable transdermal delivery of drugs.

Radio-frequency cell-ablation technology

Figure 1

RF ablation is a well-known medical technology to eliminate living cells. It is widely used to cut through tissues in minimally invasive operations or to destroy small tumors in the kidney and liver (1–5). RF ablation is performed by placing a conducting wire on a body area and passing an alternating electrical current at a frequency above 100 KHz (radio frequency) through the area. The ions in the cells adjacent to the electrodes vibrate as they try to follow the change in electrical current direction. These vibrations cause heat, which results in water evaporation and cell ablation. RF microchannels are created by placing a closely spaced array of tiny electrodes with very precise dimensions against the skin (see Figure 1). The alternating electrical current is transferred through each of the microelectrodes, ablates the cells underneath each electrode, and forms microscopic passages in the stratum corneum and outer dermis (6, 7). These RF microchannels penetrate only the outer layers of the skin, where there are no blood vessels or nerve endings. This action minimizes skin trauma and unpleasant sensations. The process is performed in seconds. Immediately after formation, the microchannels fill with interstitial fluid, which is responsible for the hydrophilic nature of the microchannels. As a result, microchannels serve as aquatic channels into the inner layers of the skin. They are embedded in the surrounding of the hydrophobic stratum corneum. For drug delivery, the microchannels may last up to 24 h. At 36 h, the delivery through treated skin returns to the values of intact skin.

A major difficulty in penetrating the skin for drug delivery is that the texture and softness of the skin change from site to site and from person to person. To address these variations, a unique microelectrode-array design was used. This microelectrode array design adapts to these differences in skin type within and between treatment sites. This design is essential to forming RF microchannels with consistent, well-controlled depths, enabling the drug to reach the capillary bed without unnecessary trauma to the inner layers of the skin (8).

Drug delivery device

Figure 2

The "ViaDerm" (TransPharma Medical Ltd., Lod, Israel) system is an example of a microelectronic system based on RF cell ablation for transdermal drug delivery. The system consists of the device, which is used to pretreat the skin and form the RF microchannels in the outer layers of the skin, and a patch containing the drug, which is placed on top of the pretreated skin (see Figure 2).